Metabolically active CD4+ T cells expressing Glut1 and OX40 preferentially harbor HIV during in vitro infection

FEBS Lett. 2017 Oct;591(20):3319-3332. doi: 10.1002/1873-3468.12843. Epub 2017 Oct 11.

Abstract

High glucose transporter 1 (Glut1) surface expression is associated with increased glycolytic activity in activated CD4+ T cells. Phosphatidylinositide 3-kinases (PI3K) activation measured by p-Akt and OX40 is elevated in CD4+Glut1+ T cells from HIV+ subjects. TCR engagement of CD4+Glut1+ T cells from HIV+ subjects demonstrates hyperresponsive PI3K-mammalian target of rapamycin signaling. High basal Glut1 and OX40 on CD4+ T cells from combination antiretroviral therapy (cART)-treated HIV+ patients represent a sufficiently metabolically active state permissive for HIV infection in vitro without external stimuli. The majority of CD4+OX40+ T cells express Glut1, thus OX40 rather than Glut1 itself may facilitate HIV infection. Furthermore, infection of CD4+ T cells is limited by p110γ PI3K inhibition. Modulating glucose metabolism may limit cellular activation and prevent residual HIV replication in 'virologically suppressed' cART-treated HIV+ persons.

Keywords: HIV; mTOR; CD4 T cells; Glut1; PI3K; cancer; immunometabolism.

Publication types

  • Letter

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / virology
  • Cell Proliferation
  • Class Ib Phosphatidylinositol 3-Kinase / genetics
  • Class Ib Phosphatidylinositol 3-Kinase / immunology
  • Gene Expression Regulation
  • Glucose Transporter Type 1 / genetics
  • Glucose Transporter Type 1 / immunology*
  • HIV Infections / drug therapy
  • HIV Infections / immunology
  • HIV Infections / metabolism*
  • HIV Infections / virology
  • HIV-1 / drug effects
  • HIV-1 / growth & development
  • Humans
  • Lymphocyte Activation
  • Male
  • Phosphoinositide-3 Kinase Inhibitors
  • Primary Cell Culture
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / immunology
  • Receptors, OX40 / genetics
  • Receptors, OX40 / immunology*
  • Signal Transduction
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / immunology
  • Virus Replication / drug effects

Substances

  • Anti-HIV Agents
  • Glucose Transporter Type 1
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors
  • Receptors, OX40
  • SLC2A1 protein, human
  • TNFRSF4 protein, human
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Class Ib Phosphatidylinositol 3-Kinase
  • PIK3CG protein, human
  • Proto-Oncogene Proteins c-akt